Exploring the complementarity of pancreatic ductal adenocarcinoma preclinical models

Purpose: Compare pancreatic ductal adenocarcinoma (PDAC), preclinical models, by their transcriptome and drug response landscapes to evaluate their complementarity. Experimental De-sign: Three paired PDAC preclinical models—patient‐derived xenografts (PDX), xenograft‐derived pancreatic organoids (XDPO) and xenograft‐derived primary cell cultures (XDPCC)—were derived from 20 patients and analyzed at the transcriptomic and chemosensitivity level. Transcriptomic characterization was performed using the basal‐like/classical subtyping and the PDAC molecular gradient (PAMG). Chemosensitivity for gemcitabine, irinotecan, 5‐fluorouracil and oxaliplatin was established and the associated biological pathways were determined using independent component analysis (ICA) on the transcriptome of each model. The selection criteria used to identify the different components was the chemosensitivity score (CSS) found for each drug in each model. Results: PDX was the most dispersed model whereas XDPO and XDPCC were mainly classical and basal-like, respectively. Chemosensitivity scoring determines that PDX and XDPO display a positive correlation for three out of four drugs tested, whereas PDX and XDPCC did not correlate. No match was observed for each tumor chemosensitivity in the different models. Finally, pathway analysis shows a significant association between PDX and XDPO for the chemosensitivity‐associated pathways and PDX and XDPCC for the chemoresistance‐associated pathways. Conclusions: Each PDAC preclinical model possesses a unique basal‐like/classical transcriptomic phenotype that strongly in-fluences their global chemosensitivity. Each preclinical model is imperfect but complementary, sug-gesting that a more representative approach of the clinical reality could be obtained by combining them. Translational Relevance: The identification of molecular signatures that underpin drug sensitivity to chemotherapy in PDAC remains clinically challenging. Importantly, the vast majority of studies using preclinical in vivo and in vitro models fail when transferred to patients in a clinical setting despite initially promising results. This study presents for the first time a comparison between three preclinical models directly derived from the same patients. We show that their applica-bility to preclinical studies should be considered with a complementary focus, avoiding tumor-based direct extrapolations, which might generate misleading conclusions and consequently the overlook of clinically relevant features.Fil: Hoare, Owen. Centre National de la Recherche Scientifique; FranciaFil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Elkaoutari, Abdessamad. Centre National de la Recherche Scientifique; FranciaFil: Gayet, Odile. Centre National de la Recherche Scientifique; FranciaFil: Bigonnet, Martin. Centre National de la Recherche Scientifique; FranciaFil: Roques, Julie. Centre National de la Recherche Scientifique; FranciaFil: Nicolle, Rémy. No especifíca;Fil: McGuckin, Colin. Cell Therapy Research Institute; FranciaFil: Forraz, Nico. Cell Therapy Research Institute; FranciaFil: Sohier, Emilie. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; FranciaFil: Tonon, Laurie. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; FranciaFil: Wajda, Pauline. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; FranciaFil: Boyault, Sandrine. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; FranciaFil: Attignon, Valéry. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; FranciaFil: Tabone, Luciana Belen. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; FranciaFil: Barbier, Sandrine. No especifíca;Fil: Mignard, Caroline. No especifíca;Fil: Duchamp, Olivier. No especifíca;Fil: Iovanna, Juan. Centre National de la Recherche Scientifique; FranciaFil: Dusetti, Nelson J.. Centre National de la Recherche Scientifique; Franci

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma

International audiencePurpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. Results: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine

The Ocean Sampling Day Consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Caractérisation de la coordination motrice des membres inférieurs lors de la marche des patients hémiparétiques

La parésie, l hyperactivité musculaire et la rétraction des tissus mous sont les principaux mécanismes physiopathologiques responsables de la dégradation de la marche dans l hémiparésie. Lors de la prise en charge du patient hémiparétique, le questionnement du clinicien s articule autour de la part de responsabilité de chaque mécanisme, et de l impact des traitements sur l organisation globale du mouvement et la qualité de la marche. L analyse de la coordination inter-segmentaire, utilisant la mesure de la phase relative continue dans le plan sagittal, apporte des éléments de réponse à cette problématique clinique. La quantité et les variations du déphasage entre les segments des membres inférieurs dans les phases du cycle de marche décrivent les stratégies de coordination motrice. Des paramètres issus de la phase relative continue inter-segmentaire, apportent des informations spécifiques quant à l origine physiopathologique des déficits cinématiques pour aider au choix du traitement, à l incidence des conditions de réentraînement de la marche, et aux bénéfices d un traitement. Cette analyse, complémentaire aux évaluations cliniques réalisées dans la pratique courante, met en évidence la restriction de possibilités de modulation par les mécanismes physiopathologiques dans le membre inférieur parétique, et des mécanismes de compensation dans le membre inférieur non-parétique. Les résultats de ce travail pourraient inciter les cliniciens à déterminer les stratégies de coordination motrice, pour définir les traitements permettant au mieux de réduire les anomalies de la marche des patients présentant une lésion motrice du système nerveux central.Paresis, muscle hyperactivity and soft tissue retraction are the main mechanisms responsible for the gait disturbance in hemiparesis. In the rehabilitation management of hemiparetic patients, clinicians try to determine the responsibility of each mechanism, and to quantify the impact of treatments on movement organization and gait efficiency. Inter-segmental coordination analysis, using measurement of the continuous relative phase in the sagittal plan, can assist in reaching these objectives. The amount of dephasing between lower limb segments, in each phase of the gait cycle, sheds light on the coordination pattern. Relevant parameters of the inter-segmental continuous relative phase may reveal specific information such as the predominance of neurological and orthopedic factors implied in the kinematic deficits, the impact of various gait rehabilitation conditions, or treatment-related benefits. This analysis, complementary to routine clinical examination, may also disclose specific motor deficits in the paretic lower limb, and compensatory strategies at work in the non-paretic lower limb. The findings reported in this thesis may encourage rehabilitation clinicians to carefully study coordination patterns, which may help define optimized treatments to lessen gait impairment in spastic paresis.VALENCIENNES-BU Sciences Lettres (596062101) / SudocSudocFranceF

Biosécurité des cultures et agroterrorisme. Une menace, des questions scientifiques et une opportunité : réactiver un dispositif d'épidémiovigilance

Les 27 et 28 novembre 2007 s’est tenu à Paris un colloque consacré à la biosécurité des cultures et à l’agroterrorisme (European Crop Biosecurity Workshop), organisé par l’INRA dans le cadre d’un projet financé par l’Union européenne (encadré 1). Nous revenons à cette occasion sur la question des risques liés à l’utilisation volontaire d’agents phytopathogènes, abordée dans un précédent article du Courrier de l’environnement de l’INRA (Suffert, 2002

Trunk's natural inclination influences stance limb kinetics, but not body kinematics, during gait initiation in able men.

The imposing mass of the trunk in relation to the whole body has an important impact on human motion. The objective of this study is to determine the influence of trunk's natural inclination--forward (FW) or backward (BW) with respect to the vertical--on body kinematics and stance limb kinetics during gait initiation.Twenty-five healthy males were divided based on their natural trunk inclination (FW or BW) during gait initiation. Instantaneous speed was calculated at the center of mass at the first heel strike. The antero-posterior impulse was calculated by integrating the antero-posterior ground reaction force in time. Ankle, knee, hip and thoraco-lumbar (L5) moments were calculated using inverse dynamics and only peaks of the joint moments were analyzed. Among all the investigated parameters, only joint moments present significant differences between the two groups. The knee extensor moment is 1.4 times higher (P<0.001) for the BW group, before the heel contact. At the hip, although the BW group displays a flexor moment 2.4 times higher (P<0.001) before the swing limb's heel-off, the FW group displays an extensor moment 3.1 times higher (P<0.01) during the swing phase. The three L5 extensor peaks after the toe-off are respectively 1.7 (P<0.001), 1.4 (P<0.001) and 1.7 (P<0.01) times higher for the FW group. The main results support the idea that the patterns described during steady-state gait are already observable during gait initiation. This study also provides reference data to further investigate stance limb kinetics in specific or pathologic populations during gait initiation. It will be of particular interest for elderly people, knowing that this population displays atypical trunk postures and present a high risk of falling during this forward stepping

Correction of polydactyly in patients with Ellis-van Creveld syndrome: a report of two cases

Ellis-van Creveld syndrome (EVC) is a rare chondroectodermal dysplasia presenting several skeletal manifestations and congenital heart malformations. Polydactyly is the most frequent skeletal anomaly. The authors report two cases of EVC syndrome with different manifestations, which underwent surgical treatment for polydactyly

A methodology for assessing the risk posed by the deliberate and harmful use of plant pathogens in Europe

Deliberate and malevolent use of plant pathogens, i.e. agroterrorism lato sensu (anticrop bioterrorism and use of bioweapons against the agricultural sector), may represent a non-negligible threat for crops and forests in Europe. In order to assess this risk objectively, a methodology based on a critical review of existing Pest Risk Analysis schemes has been elaborated and is described in the present paper. In this methodology, three interdependent steps are suggested: (i) definition of an a priori list of potentially dangerous plant pathogens for Europe, (ii) detailed elaboration and analysis of theoretical scenarios of possible acts of agroterrorism, and (iii) elaboration and use of a risk assessment scheme adapted to agroterroris